Filtern
Erscheinungsjahr
- 2021 (2297)
- 2020 (1885)
- 2019 (1583)
- 2018 (1470)
- 2017 (1220)
- 2022 (1184)
- 2016 (1083)
- 2012 (1006)
- 2014 (1000)
- 2013 (991)
- 2010 (970)
- 2008 (949)
- 2009 (939)
- 2015 (907)
- 2011 (893)
- 2006 (758)
- 2005 (756)
- 2007 (749)
- 2004 (640)
- 2023 (559)
- 2002 (513)
- 2003 (508)
- 2001 (422)
- 2000 (385)
- 1999 (314)
- 1998 (309)
- 1995 (306)
- 1996 (288)
- 1997 (288)
- 1993 (264)
- 1994 (251)
- 1992 (221)
- 2024 (169)
- 1991 (165)
- 1990 (153)
- 1989 (145)
- 1988 (141)
- 1987 (134)
- 1985 (119)
- 1986 (115)
- 1983 (103)
- 1981 (90)
- 1984 (88)
- 1982 (85)
- 1976 (57)
- 1980 (53)
- 1974 (51)
- 1913 (50)
- 1972 (50)
- 1969 (46)
- 1966 (42)
- 1977 (42)
- 1968 (40)
- 1975 (39)
- 1979 (39)
- 1898 (38)
- 1967 (37)
- 1978 (37)
- 1885 (36)
- 1965 (35)
- 1971 (35)
- 1973 (35)
- 1893 (34)
- 1970 (34)
- 1901 (32)
- 1908 (32)
- 1895 (31)
- 1914 (30)
- 1962 (30)
- 1964 (30)
- 1889 (29)
- 1904 (29)
- 1963 (29)
- 1911 (28)
- 1891 (27)
- 1896 (27)
- 1907 (26)
- 1894 (25)
- 1897 (24)
- 1960 (24)
- 1909 (23)
- 1915 (23)
- 1957 (23)
- 1899 (22)
- 1903 (22)
- 1926 (22)
- 1933 (22)
- 1947 (22)
- 1902 (21)
- 1905 (21)
- 1912 (21)
- 1927 (21)
- 1930 (21)
- 1881 (20)
- 1883 (20)
- 1900 (20)
- 1934 (20)
- 1884 (19)
- 1890 (19)
- 1910 (19)
- 1923 (19)
- 1938 (19)
- 1917 (18)
- 1924 (18)
- 1925 (18)
- 1931 (18)
- 1956 (18)
- 1959 (18)
- 1887 (17)
- 1892 (17)
- 1906 (17)
- 1918 (17)
- 1921 (17)
- 1922 (17)
- 1929 (17)
- 1937 (17)
- 1877 (16)
- 1882 (16)
- 1961 (16)
- 1919 (15)
- 1920 (15)
- 1958 (15)
- 1872 (14)
- 1886 (14)
- 1888 (14)
- 1916 (14)
- 1954 (14)
- 1873 (13)
- 1876 (13)
- 1880 (13)
- 1935 (13)
- 1936 (13)
- 1859 (12)
- 1861 (12)
- 1928 (12)
- 1939 (12)
- 1953 (12)
- 1868 (11)
- 1875 (11)
- 1857 (10)
- 1862 (10)
- 1866 (10)
- 1848 (9)
- 1858 (9)
- 1879 (9)
- 1950 (9)
- 1952 (9)
- 1854 (8)
- 1856 (8)
- 1867 (8)
- 1870 (8)
- 1878 (8)
- 1932 (8)
- 1949 (8)
- 1951 (8)
- 1844 (7)
- 1853 (7)
- 1869 (7)
- 1871 (7)
- 1940 (7)
- 1942 (7)
- 1948 (7)
- 1842 (6)
- 1843 (6)
- 1845 (6)
- 1850 (5)
- 1863 (5)
- 1941 (5)
- 1955 (5)
- 1855 (4)
- 1864 (4)
- 1865 (4)
- 1874 (4)
- 1946 (4)
- 1804 (3)
- 1815 (3)
- 1818 (3)
- 1828 (3)
- 1829 (3)
- 1832 (3)
- 1834 (3)
- 1835 (3)
- 1839 (3)
- 1849 (3)
- 1852 (3)
- 1860 (3)
- 1752 (2)
- 1761 (2)
- 1777 (2)
- 1785 (2)
- 1803 (2)
- 1806 (2)
- 1810 (2)
- 1812 (2)
- 1817 (2)
- 1820 (2)
- 1822 (2)
- 1825 (2)
- 1826 (2)
- 1830 (2)
- 1836 (2)
- 1840 (2)
- 1841 (2)
- 1943 (2)
- 0222 (1)
- 1692 (1)
- 1734 (1)
- 1740 (1)
- 1762 (1)
- 1767 (1)
- 1778 (1)
- 1780 (1)
- 1800 (1)
- 1801 (1)
- 1805 (1)
- 1807 (1)
- 1816 (1)
- 1823 (1)
- 1824 (1)
- 1833 (1)
- 1837 (1)
- 1838 (1)
- 1846 (1)
- 1851 (1)
- 1945 (1)
Dokumenttyp
- Wissenschaftlicher Artikel (30051) (entfernen)
Sprache
- Englisch (15256)
- Deutsch (12926)
- Portugiesisch (584)
- Französisch (385)
- Kroatisch (251)
- Spanisch (242)
- Italienisch (131)
- Türkisch (101)
- Latein (35)
- Mehrsprachig (35)
Volltext vorhanden
- ja (30051)
Gehört zur Bibliographie
- nein (30051) (entfernen)
Schlagworte
- Deutsch (482)
- taxonomy (425)
- Literatur (282)
- Hofmannsthal, Hugo von (184)
- new species (181)
- Rezeption (155)
- Filmmusik (154)
- Übersetzung (135)
- Vormärz (113)
- Johann Wolfgang von Goethe (107)
Institut
- Medizin (5165)
- Physik (1745)
- Biowissenschaften (1115)
- Biochemie und Chemie (1108)
- Extern (1069)
- Gesellschaftswissenschaften (799)
- Frankfurt Institute for Advanced Studies (FIAS) (705)
- Geowissenschaften (582)
- Präsidium (453)
- Philosophie (448)
Background and Objectives: Proteins of the coagulation system contribute to autoimmune inflammation in patients with multiple sclerosis (MS). On blood-brain barrier (BBB) disruption, fibrinogen enters the CNS and is rapidly converted to fibrin, unfolding pleiotropic autoimmune mechanisms. Fibrin accumulation leads to subsequent proteolytic degradation that results in D-dimer generation. The primary objective of this study was to determine intrathecal levels of D-dimer in CSF as a measure of intrathecal coagulation cascade activation and to evaluate its diagnostic utility in patients with MS in contrast to healthy subjects. Key secondary objectives included analysis of CSF D-dimer in differential diagnoses of MS and its relation to routine clinical markers of disease activity.
Methods: Patients admitted for the assessment of suspected MS were prospectively recruited from October 2017 to December 2020. Blood plasma and citrated CSF samples were analyzed using a highly sensitive luminescent oxygen channeling immunoassay. Intrathecal generation of D-dimer was analyzed by adjusting for CSF/serum albumin (Qalb) and CSF/plasma D-dimer quotients (QD-dimer), and corresponding CSF fibrinogen levels were determined. Final diagnoses after full evaluation and clinical data were recorded.
Results: Of 187 patients, 113 patients received a diagnosis of MS or clinically/radiologically isolated syndrome. We found increased intrathecal CSF D-dimer generation levels (QD-dimer/Qalb-index) for patients with relapsing-remitting MS (RRMS; n = 71, median 4.7, interquartile range [IQR] 2.5–8.0) when compared with those for disease controls (n = 22, median 2.6, IQR 2.1–4.8, p = 0.031). Absolute CSF D-dimer values correlated with CSF fibrinogen levels (r = 0.463; p < 0 .001) and CSF leukocytes (r = 0.273; p = 0.003) and were elevated in MS patients with contrast enhancement (CE) compared with MS patients without CE on MRI (n = 48, median 6 ng/mL, and IQR 3–15.25 vs n = 41, median 4 ng/mL, and IQR 2–7; p = 0.026). Exploratory subgroup analyses indicated a correlation of intrathecal inflammatory activity and CSF D-dimer levels.
Discussion: D-dimer in CSF can be reliably determined and correlates with markers of CNS inflammation and CSF fibrinogen levels. Adjusted for BBB dysfunction, CSF D-dimer may allow the identification of intrathecal coagulation cascade activation in patients with MS.
Classification of Evidence: This study provides Class I evidence that CSF D-dimer levels are elevated in patients with RRMS.
Nanoplastics affect the inflammatory cytokine release by primary human monocytes and dendritic cells
(2022)
So far, the human health impacts of nano- and microplastics are poorly understood. Thus, we investigated whether nanoplastics exposure induces inflammatory processes in primary human monocytes and monocyte-derived dendritic cells. We exposed these cells in vitro to nanoplastics of different shapes (irregular vs. spherical), sizes (50–310 nm and polydisperse mixtures) and polymer types (polystyrene; polymethyl methacrylate; polyvinyl chloride, PVC) using concentrations of 30–300 particles cell−1. Our results show that irregular PVC particles induce the strongest cytokine release of these nanoplastics. Irregular polystyrene triggered a significantly higher pro-inflammatory response compared to spherical nanoplastics. The contribution of chemicals leaching from the particles was minor. The effects were concentration-dependent but varied markedly between cell donors. We conclude that nanoplastics exposure can provoke human immune cells to secrete cytokines as key initiators of inflammation. This response is specific to certain polymers (PVC) and particle shapes (fragments). Accordingly, nanoplastics cannot be considered one homogenous entity when assessing their health implications and the use of spherical polystyrene nanoplastics may underestimate their inflammatory effects.
There has been a renewed interest in the potential use of psychedelics for the treatment of psychiatric conditions. Nevertheless, little is known about the mechanism of action and molecular pathways influenced by ayahuasca use in humans. Therefore, for the first time, our study aims to investigate the human metabolomics signature after consumption of a psychedelic, ayahuasca, and its connection with both the psychedelic-induced subjective effects and the plasma concentrations of ayahuasca alkaloids.
Plasma samples of 23 individuals were collected both before and after ayahuasca consumption. Samples were analysed through targeted metabolomics and further integrated with subjective ratings of the ayahuasca experience (i.e., using the 5-Dimension Altered States of Consciousness Rating Scale [ASC]), and plasma ayahuasca-alkaloids using integrated network analysis. Metabolic pathways enrichment analysis using diffusion algorithms for specific KEGG modules was performed on the metabolic output.
Compared to baseline, the consumption of ayahuasca increased N-acyl-ethanolamine endocannabinoids, decreased 2-acyl-glycerol endocannabinoids, and altered several large-neutral amino acids (LNAAs). Integrated network results indicated that most of the LNAAs were inversely associated with 9 out of the 11 subscales of the ASC, except for tryptophan which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with the ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in several pathways involved in neurotransmission such as serotonin and dopamine synthesis.
In conclusion, a crosstalk between the circulating LNAAs and the subjective effects is suggested, which is independent of the alkaloid concentrations and provides insights into the specific metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Pathologies associated with tissue ischemia/reperfusion (I/R) in highly metabolizing organs such as the brain and heart are leading causes of death and disability in humans. Molecular mechanisms underlying mitochondrial dysfunction during acute injury in I/R are tissue-specific, but their details are not completely understood. A metabolic shift and accumulation of substrates of reverse electron transfer (RET) such as succinate are observed in tissue ischemia, making mitochondrial complex I of the respiratory chain (NADH:ubiquinone oxidoreductase) the most vulnerable enzyme to the following reperfusion. It has been shown that brain complex I is predisposed to losing its flavin mononucleotide (FMN) cofactor when maintained in the reduced state in conditions of RET both in vitro and in vivo. Here we investigated the process of redox-dependent dissociation of FMN from mitochondrial complex I in brain and heart mitochondria. In contrast to the brain enzyme, cardiac complex I does not lose FMN when reduced in RET conditions. We proposed that the different kinetics of FMN loss during RET is due to the presence of brain-specific long 50 kDa isoform of the NDUFV3 subunit of complex I, which is absent in the heart where only the canonical 10 kDa short isoform is found. Our simulation studies suggest that the long NDUFV3 isoform can reach toward the FMN binding pocket and affect the nucleotide affinity to the apoenzyme. For the first time, we demonstrated a potential functional role of tissue-specific isoforms of complex I, providing the distinct molecular mechanism of I/R-induced mitochondrial impairment in cardiac and cerebral tissues. By combining functional studies of intact complex I and molecular structure simulations, we defined the critical difference between the brain and heart enzyme and suggested insights into the redox-dependent inactivation mechanisms of complex I during I/R injury in both tissues.
"High-aluminous coal" is an important coal kind and widely distributed in North China in age of Permo-Carboniferous period. To explore their occurrence state, a total of 15 harmful elements (Li, Ga, In, Cd, Cr, Pb, Be, Mn, Zn, Ag, Co, Ni, Cu, Ba and U) in the No.9 coal and No.11 coal collected from Pingshuo mining district were determined by inductively coupled plasma mass spectrometry (ICP-MS) and scanning electron microscope with energy spectrum (SEM-EDX). The results showed that the content of Li, Ga, In, Pb, Ag and U were all exceed the world hard coal. In view of the result of clustering analysis within trace elements, it was found that Co, Ni, Zn, Cu, Ag and Cr were mainly associated with sulfide minerals due to their common sulfophilic property. Manganese was mainly occurred in carbonate minerals, while Ba, Cd and U were mainly associated with total minerals. In addition, Pb was related to sulfides and Be is mainly distributed in clay minerals. The enrichment of such harmful elements in Pingshuo coal was caused by the combined effect of transgression and input of terrestrial materials in the peat accumulation stage. Li, Ga, In and Ag have reached the harmful grade.
Objectives: To investigate whether citizens’ adherence to health-protective non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic is predicted by identity leadership, wherein leaders are perceived to create a sense of shared national identity.
Design: Observational two-wave study. Hypotheses testing was conducted with structural equation modelling.
Setting: Data collection during the COVID-19 pandemic in China, Germany, Israel and the USA in April/May 2020 and four weeks later.
Participants: Adults in China (n=548, 66.6% women), Germany (n=182, 78% women), Israel (n=198, 51.0% women) and the USA (n=108, 58.3% women).
Measures: Identity leadership (assessed by the four-item Identity Leadership Inventory Short-Form) at Time 1, perceived shared national identification (PSNI; assessed with four items) and adherence to health-protective NPIs (assessed with 10 items that describe different health-protective interventions; for example, wearing face masks) at Time 2.
Results: Identity leadership was positively associated with PSNI (95% CI0.11 to 0.30, p<0.001) in all countries. This, in turn, was related to more adherence to health-protective NPIs in all countries (95% CI 0.03 to 0.36, 0.001≤p≤0.017) except Israel (95% CI−0.03 to 0.27, p=0.119). In Germany, the more people saw Chancellor Merkel as engaging in identity leadership, the more they adhered to health-protective NPIs (95% CI 0.04 to 0.18, p=0.002). In the USA, in contrast, the more people perceived President Trump as engaging in identity leadership, the less they adhered to health-protective NPIs (95% CI−0.17 to −0.04, p=0.002).
Conclusions: National leaders can make a difference by promoting a sense of shared identity among their citizens because people are more inclined to follow health-protective NPIs to the extent that they feel part of a united ‘us’. However, the content of identity leadership (perceptions of what it means to be a nation’s citizen) is essential, because this can also encourage people to disregard such recommendations.
Patients with coronavirus disease 19 (COVID-19) commonly show abnormalities of liver tests (LTs) of undetermined cause. Considering drugs as tentative culprits, the current systematic review searched for published COVID-19 cases with suspected drug-induced liver injury (DILI) and established diagnosis using the diagnostic algorithm of RUCAM (Roussel Uclaf Causality Assessment Method). Data worldwide on DILI cases assessed by RUCAM in COVID-19 patients were sparse. A total of 6/200 reports with initially suspected 996 DILI cases in COVID-19 patients and using all RUCAM-based DILI cases allowed for a clear description of clinical features of RUCAM-based DILI cases among COVID-19 patients: (1) The updated RUCAM published in 2016 was equally often used as the original RUCAM of 1993, with both identifying DILI and other liver diseases as confounders; (2) RUCAM also worked well in patients treated with up to 18 drugs and provided for most DILI cases a probable or highly probable causality level for drugs; (3) DILI was preferentially caused by antiviral drugs given empirically due to their known therapeutic efficacy in other virus infections; (4) hepatocellular injury was more often reported than cholestatic or mixed injury; (5) maximum LT values were found for alanine aminotransferase (ALT) 1.541 U/L and aspartate aminotransferase (AST) 1.076 U/L; (6) the ALT/AST ratio was variable and ranged from 0.4 to 1.4; (7) the mean or median age of the COVID-19 patients with DILI ranged from 54.3 to 56 years; (8) the ratio of males to females was 1.8–3.4:1; (9) outcome was favorable for most patients, likely due to careful selection of the drugs and quick cessation of drug treatment with emerging DILI, but it was fatal in 19 patients; (10) countries reporting RUCAM-based DILI cases in COVID-19 patients included China, India, Japan, Montenegro, and Spain; (11) robust estimation of the percentage contribution of RUCAM-based DILI for the increased LTs in COVID-19 patients is outside of the current scope. In conclusion, RUCAM-based DILI with its clinical characteristics in COVID-19 patients and its classification as a confounding variable is now well defined, requiring a new correct description of COVID-19 features by removing DILI characteristics as confounders.